The overall objective of consortium planning is to propose studies to develop new strategies to convert human pluripotent stem cells and somatic cells into hematopoietic (HSCs) and cardiac stem cells (CSCs), through identification of genetic and epigenetic programs leading to formation of pre-HSCs and pre-CSCs and activation of self-renewal program in lineage-restricted cells. Here we combine expertise in basic biology of pluripotent stem cells (Thomson), hematopoietic differentiation (Slukvin) and cardiac differentiation (Kamp), and artificial transcription factors (Ansari) at University of Wisconsin to advance our understanding of HSC and CSC development in humans and develop artificial transcription factor (ATF)-based technologies to generate HSCs and CSCs. We propose the following projects: Project 1) Determine the most critical molecular and cellular events leading to formation of engraftable HSCs and CSCs derived from human pluripotent stem cells. Project 2) Develop artificial transcription factor (ATF)-based technology to convert human pluripotent stem cells and fibroblasts into HSCs and CSCs. The proposed studies will provide new insights into how the hematopoietic and cardiac cells develop in humans, and could ultimately lead to novel and scalable cell source of HSCs and CSCs for therapies of blood cancer and cardiovascular diseases.